The authors state that they have no conflicts of interest.
Association Analysis of WNT10B With Bone Mass and Structure Among Individuals of African Ancestry†
Version of Record online: 3 NOV 2008
Copyright © 2009 ASBMR
Journal of Bone and Mineral Research
Volume 24, Issue 3, pages 437–447, March 2009
How to Cite
Zmuda, J. M., Yerges, L. M., Kammerer, C. M., Cauley, J. A., Wang, X., Nestlerode, C. S., Wheeler, V. W., Patrick, A. L., Bunker, C. H., Moffett, S. P. and Ferrell, R. E. (2009), Association Analysis of WNT10B With Bone Mass and Structure Among Individuals of African Ancestry. J Bone Miner Res, 24: 437–447. doi: 10.1359/jbmr.081106
- Issue online: 4 DEC 2009
- Version of Record online: 3 NOV 2008
- Manuscript Accepted: 28 OCT 2008
- Manuscript Revised: 9 OCT 2008
- Manuscript Received: 17 MAR 2008
Wnts comprise a family of secreted growth factors that regulate the development and maintenance of many organs. Recently, Wnt10b was shown to stimulate osteoblastogenesis and bone formation in mice. To evaluate further the role of Wnt10b in bone health in humans, we performed bidirectional sequencing of ∼8 kb of the WNT10B gene region in 192 individuals (96 African, 96 white) to identify single nucleotide polymorphisms (SNPs). We identified 19 SNPs with minor allele frequency (MAF) ≥0.01. Ten of these SNPs were not present in the NCBI dbSNP database (build 127), whereas 10 of the 20 SNPs (50%) reported in dbSNP were not verified. We initially genotyped seven tagging SNPs that captured common (MAF ≥ 0.05) variation in the region with r2 > 0.80 and a potentially functional SNP in exon 5 in 1035 Afro-Caribbean men ≥40 yr of age. Association analysis showed three SNPs in a 3′ region of linkage disequilibrium that were associated with DXA measures of hip BMD. Associations between two of these three SNPs (rs1051886, rs3741627) with hip BMD were replicated in an additional 980 Afro-Caribbean men (p < 0.05), in the combined sample of 2015 men (p ≤ 0.006), and in 416 individuals ≥18 yr of age (mean, 44 yr) belonging to eight extended, multigenerational Afro-Caribbean families with mean family size >50 (3535 relative pairs; p < 0.05). Further analysis showed that rs1051886 and rs3741627 were associated with cortical cross-sectional area, periosteal circumference, and BMC in the radius, such that individuals with the minor alleles had lower biomechanical indices of long-bone bending strength. This analysis implicates the WNT10B locus as a genetic element in the regulation of bone mass and structural geometry.